IC50-EC50-定义及区别

IC50TheIC50isameasureoftheeffectivenessofacompoundininhibitingbiologicalorbiochemicalfunction.Often,thecompoundinquestionisadrugcandidate.Thisquantitativemeasureindicateshowmuchofaparticulardrugorothersubstance(inhibitor)isneededtoinhibitagivenbiologicalprocess(orcomponentofaprocess,i.e.anenzyme,cell,cellreceptorormicroorganism)byhalf.Inotherwords,itisthehalfmaximal(50%)inhibitoryconcentration(IC)ofasubstance(50%IC,orIC50).Itiscommonlyusedasameasureofantagonistdrugpotencyinpharmacologicalresearch.Sometimes,itisalsoconvertedtothepIC50scale(-logIC50),inwhichhighervaluesindicateexponentiallygreaterpotency.AccordingtotheFDA,IC50representstheconcentrationofadrugthatisrequiredfor50%inhibitioninvitro.ItiscomparabletoanEC50foragonistdrugs.EC50alsorepresentstheplasmaconcentrationrequiredforobtaining50%ofamaximumeffectinvivo.DeterminationIC50ofadrugFunctionalantagonistassay:TheIC50ofadrugcanbedeterminedconstructingadose-responsecurveandexaminingtheeffectofdifferentconcentrationsofantagonistonreversingagonistactivity.IC50valuescanbecalculatedforagivenantagonistbydeterminingtheconcentrationneededtoinhibithalfofthemaximumbiologicalresponseoftheagonist.IC50valuesaredependentonconditionsunderwhichtheyaremeasured.Ingeneral,thehighertheconcentrationofinhibitor,themorewillagonistactivitybelowered.IC50valueincreasesasenzymeconcentrationincreases.FurthermoredependingonthetypeofinhibitionotherfactorsmayinfluenceIC50value;forATPdependentenzymesIC50valuehasaninterdependencywithconcentrationofATP,especiallysoifinhibitionisallofitcompetitive.IC50valuescanbeusedtocomparethepotencyoftwoantagonists.Competitionbindingassays:Inthistypeofassay,asingleconcentrationofradioligand(usuallyanagonist)isusedineveryassaytube.Theligandisusedatalowconcentration,usuallyatorbelowitsKDvalue.Thelevelofspecificbindingoftheradioligandisthendeterminedinthepresenceofarangeofconcentrationsofothercompetingnon-radioactivecompounds(usuallyantagonists),inordertomeasurethepotencywithwhichtheycompeteforthebindingoftheradioligand.Competitioncurvesmayalsobecomputer-fittedtoalogisticfunctionasdescribedunderdirectfit.InthissituationtheIC50istheconcentrationofcompetingligandwhichdisplaces50%ofthespecificbindingoftheradioligand.TheIC50valueisconvertedtoanabsoluteinhibitionconstantKi)usingtheCheng-Prusoffequation(seeKi).IC50andaffinity:IC50isnotadirectindicatorofaffinityalthoughthetwocanberelatedatleastforcompetitiveagonistsandantagonistsbytheCheng-Prusoffeqtn.whereKiisthebindingaffinityoftheinhibitor,IC50isthefunctionalstrengthoftheinhibitor,[S]issubstrateconcentrationandKmistheaffinityofthesubstratefortheenzyme.WhereastheIC50valueforacompoundmayvarybetweenexperimentsdependingonradioligandconcentration,theKiisanabsolutevalue.Kiistheinhibitionconstantforadrug;theconcentrationofcompetingligandinacompetitionassaywhichwouldoccupy50%ofthereceptorsifnoradioligandwerepresent.----------------------------------------------------ECxConcentrationhavinganeffectonx%ofthepopulationcomparedtocontrolEC50EffectConcentration50%orconcentrationhaving50%ofeffectcomparedtocontrolLCxconcentrationhavingcausedthedeathofX%ofthepopulationtestedcomparedtocontrolIC50InhibitionConcentration50%orconcentrationinhibitingof50%aparameterlikethegrowthorluminescencecomparedtocontrolLC50concentrationhavingcausedthedeathof50%ofthepopulationtestedcomparedtocontrolLD50LethalProportions50%orproportionshavingcausedthedeathof50%ofthepopulationtested.ED50“50%medianeffectivedose”LOECLowObservedEffectConcentrationorconcentrationwithaveryweakobservableeffect.Itisaboutthelowestconcentrationforwhichtheeffectisdifferentfromthatofcontrols.ItisthefirstconcentrationtestedaftertheNOEC.NOECNoObservedEffectConcentrationorconcentrationwithoutobservableeffect.Itisaboutthehighestconcentrationtestedforwhichtheeffectissignificantlynotdifferentfromcontrols